Table 2.
Cox analysis of clinical baseline characteristics, tumor laterality and FPR in 2917 stage I–IV colorectal cancer patients.
| Stage | Comparison | RFS (HR and 95% CI) | OS (HR and 95% CI) | ||||
|---|---|---|---|---|---|---|---|
| p-value* | Crude | Adjusted | p-value* | Crude | Adjusted | ||
| Stage I | Male versus female | 0.109 | 1.823 (0.875–3.795) | 2.017 (0.514–7.908) | 0.235 | 2.165 (0.586–7.996) | 3.023 (0.379–24.114) |
| Age (⩾60 versus <60) | 0.131 | 1.970 (0.818–4.745) | 2.750 (0.71910.524) | 0.080 | 3.035 (0.822–11.211) | 8.096 (0.625–40.337) | |
| Smoking (yes versus no) | 0.404 | 2.364 (0.313–17.824) | 1.592 (0.162–15.610) | 0.894 | 1.155 (0.139–9.596) | 1.561 (0.042–58.342) | |
| Drinking (yes versus no) | 0.939 | 1.060 (0.242–4.634) | 1.971 (0.039–100.734) | 0.798 | 1.317 (0.158–10.936) | 1.526 (0.117–19.874) | |
| Diabetes (yes versus no) | 0.716 | 1.314 (0.301–5.748) | 2.321 (0.458–11.768) | 0.079 | 3.904 (0.757–20.126) | 4.418 (0.759–25.718) | |
| Hypertension (yes versus no) | 0.774 | 1.200 (0.345–4.176) | 1.292 (0.290–5.754) | 0.299 | 2.323 (0.451–11.973) | 1.420 (0.208–9.701) | |
| T2 versus T1 | 0.278 | 1.688 (0.655–4.351) | 2.327 (0.285–18.960) | 0.247 | 3.142 (0.406–24.338) | 1.532 (0.063–37.192) | |
| Size (⩾5 versus <5) | 0.527 | 1.386 (0.504–3.814) | 1.398 (0.155–12.609) | 0.104 | 2.733 (0.771–9.687) | 6.579 (0.581–7.692) | |
| Differentiation (G1-2 versus G3-4) | 0.555 | 1.629 (0.352–7.519) | 4.150 (0.383–44.950) | 0.529 | 1.629 (0.352–7.519) | 8.932 (0.576–13.861) | |
| CEA (⩾5 versus <5) | 0.004 | 4.244 (1.569–11.479) | 5.668 (1.628–19.729) | 0.009 | 5.814 (1.301–25.995) | 6.988 (1.402–34.841) | |
| CA199 (⩾37 versus <37)) | 0.592 | 2.126 (0.100–15.326) | 2.238 (0.124–4.339) | 0.605 | 2.128 (0.352–18.653) | 2.345 (0.259–16.554) | |
| Tumor location (Right versus left) | 0.622 | 1.347 (0.413–4.399) | 1.999 (0.229–17.436) | 0.579 | 1.532 (0.336–6.992) | 5.444 (0.251–11.784) | |
| High-FPR versus low-FPR | <0.001 | 6.245 (2.287–17.051) | 6.833 (1.438–32.466) | 0.007 | 6.535 (1.357–31.459) | 6.548 (1.229–30.447) | |
| Stage II | Male versus Female | 0.890 | 1.019 (0.782–1.327) | 1.047 (0.620–1.768) | 0.476 | 1.138 (0.797–1.625) | 1.303 (0.653–2.598) |
| Age (⩾60 versus <60) | 0.002 | 1.673 (1.208–2.317) | 1.075 (0.523–2.212) | <0.001 | 2.211 (1.490–3.280) | 1.147 (0.473–2.779) | |
| Smoking (yes versus no) | 0.749 | 1.074 (0.694–1.661) | 1.109 (0.625–1.968) | 0.753 | 1.095 (0.619–1.937) | 1.351 (0.659–2.769) | |
| Drinking (yes versus no) | 0.602 | 1.143 (0.690–1.893) | 1.281 (0.529–3.106) | 0.301 | 1.462 (0.707–3.021) | 2.197 (0.684–7.058) | |
| Diabetes (yes versus no) | 0.583 | 1.187 (0.642–2.193) | 1.274 (0.548–2.964) | 0.129 | 1.692 (0.850–3.368) | 1.287 (0.451–3.668) | |
| Hypertension (yes versus no) | 0.499 | 1.181 (0.730–1.910) | 1.093 (0.586–2.038) | 0.965 | 1.013 (0.563–1.824) | 1.138 (0.514–2.518) | |
| Chemotherapy (yes versus no) | 0.077 | 0.775 (0.583–1.030) | 0.559 (0.44–0.909) | 0.001 | 0.545 (0.381–0.779) | 0.506 (0.273–0.936) | |
| Radiotherapy (yes versus no) | 0.017 | 0.537 (0.319–0.904) | 0.305 (0.152–0.610) | 0.486 | 0.760 (0.350–1.650) | 0.275 (0.113–0.672) | |
| T4 versus T3 | 0.002 | 1.505 (1.163–1.948) | 1.137 (0.504–2.567) | 0.124 | 1.306 (0.928–1.838) | 1.411 (0.514–3.874) | |
| Size (⩾5 versus <5) | 0.360 | 1.159 (0.844–1.594) | 1.177 (0.714–1.942) | 0.344 | 1.211 (0.813–1.805) | 1.394 (0.732–2.653) | |
| Differentiation (G1-2 versus G3-4) | 0.185 | 1.531 (0.810–2.894) | 2.853 (0.102–9.075) | 0.001 | 2.870 (1.496–5.505) | 3.139 (0.945–6.544) | |
| CEA (⩾5 versus <5) | 0.005 | 1.686 (1.169–2.433) | 1.032 (0.616–1.729) | 0.013 | 1.756 (1.121–2.753) | 2.513 (1.198–5.272) | |
| CA199 (⩾37 versus <37)) | 0.006 | 1.800 (1.177–2.753) | 2.140 (1.247–3.672) | 0.001 | 2.240 (1366–3.674) | 2.078 (1.040–4.154) | |
| Tumor location (right versus left) | 0.230 | 1.184 (0.897–1.52) | 1.068 (0.608–1.874) | 0.371 | 1.181 (0.819–1.704) | 1.394 (0.695–2.797) | |
| High-FPR versus low-FPR | <0.001 | 3.144 (2.267–4.361) | 3.431 (2.102–5.601) | <0.001 | 4.756 (2.985–7.579) | 7.194 (3.329–15.547) | |
| Stage III | Male versus female | 0.444 | 1.082 (0.882–1.328) | 1.024 (0.746–1.404) | 0.713 | 1.050 (0.808–1.366) | 1.250 (0.834–1.875) |
| Age (⩾60 versus <60) | 0.999 | 1.000 (0.820–1.220) | 1.089 (0.794–1.492) | 0.013 | 1.383 (1.069–1.790) | 1.805 (1.192–2.734) | |
| Smoking (yes versus no) | 0.949 | 1.010 (0.736–1.386) | 1.039 (0.670–1.612) | 0.381 | 1.214 (0.784–1.878) | 1.081 (0.584–2.001) | |
| Drinking (yes versus no) | 0.876 | 1.028 (0.720–1.469) | 1.049 (0.663–1.660) | 0.629 | 1.124 (0.699–1.806) | 1.023 (0.474–2.211) | |
| Diabetes (yes versus no) | 0.058 | 1.539 (0.978–2.422) | 1.467 (0.832–2.586) | 0.051 | 1.862 (0.985–3.521) | 2.339 (0.946–5.782) | |
| Hypertension (yes versus no) | 0.061 | 1.364 (0.982–1.896) | 1.481 (0.969–2.262) | 0.271 | 1.255 (0.835–1.888) | 1.257 (0.713–2.216) | |
| Chemotherapy (yes versus no) | 0.040 | 0.755 (0.575–0.991) | 0.743 (0.493–1.118) | <0.001 | 0.548 (0.395–0.760) | 0.607 (0.360–1.024) | |
| Radiotherapy (yes versus no) | 0.077 | 0.741 (0.529–1.038) | 1.216 (0.764–1.936) | 0.244 | 0.725 (0.420–1.251) | 0.704 (0.298–1.660) | |
| T3-4 versus T1-2 | <0.001 | 3.440 (2.018–5.865) | 2.662 (1.244–5.694) | <0.001 | 4.601 (2.045–10.351) | 4.308 (1.054–17.600) | |
| Size (⩾5 versus <5) | 0.532 | 1.074 (0.856–1.348) | 1.103 (0.813–1.496) | 0.016 | 1.414 (1.062–1.882) | 1.292 (0.862–1.937) | |
| Differentiation (G1-2 versus G3-4) | 0.014 | 1.463 (1.077–1.989) | 1.295 (0.884–1.899) | 0.031 | 1.564 (1.036–2.361) | 1.198 (0.695–2.067) | |
| CEA (⩾5 versus <5) | <0.001 | 1.553 (1.224–1.970) | 1.341 (0.999–1.801) | <0.001 | 1.785 (1.312–2.428) | 1.362 (0.910–2.038) | |
| CA199 (⩾37 versus <37)) | 0.001 | 1.787 (1.372–2.327) | 1.455 (1.053–2.010) | <0.001 | 2.436 (1.767–3.360) | 1.889 (1.243–2.869) | |
| Tumor location (right versus left) | 0.006 | 1.370 (1.093–1.716) | 1.173 (0.831–1.655) | 0.014 | 1.430 (1.071–1.910) | 1.283 (0.817–2.013) | |
| High-FPR versus low-FPR | <0.001 | 2.439 (1.947–3.056) | 2.182 (1.616–2.947) | <0.001 | 2.761 (2.079–3.666) | 2.808 (1.858–4.241) | |
| Stage IV | Male versus female | 0.747 | 1.032 (0.845–1.261) | 1.244 (0.723–2.139) | 0.269 | 1.099 (0.926–1.305) | 1.204 (0.749–1.934) |
| Age (⩾60 versus <60) | 0.097 | 1.324 (0.939–1.866) | 1.148 (0.483–2.729) | <0.001 | 1.713 (1.333–2.201) | 1.548 (0.785–3.054) | |
| Smoking (yes versus no) | 0.200 | 1.210 (0.895–1.636) | 1.111 (0.263–4.692) | 0.673 | 1.049 (0.837–1.313) | 1.261 (0.554–2.868) | |
| Drinking (yes versus no) | 0.023 | 1.439 (1.039–1.992) | 2.851 (0.860–9.446) | 0.195 | 1.175 (0.915–1.508) | 1.096 (0.399–3.010) | |
| Diabetes (yes versus no) | 0.824 | 1.040 (0.727–1.488) | 2.652 (0.793–8.865) | 0.437 | 1.142 (0.810–1.610) | 1.368 (0.152–9.846) | |
| Hypertension (yes versus no) | 0.514 | 1.099 (0.821–1.471) | 1.603 (0.792–3.247) | 0.639 | 1.062 (0.823–1.371) | 1.499 (0.744–3.021) | |
| Palliative operation (yes versus no) | 0.016 | 0.788 (0.644–0.963) | 0.779 (0.315–1.923) | <0.001 | 0.588 (0.495–0.699) | 0.818 (0.315–2.122) | |
| Chemotherapy (yes versus no) | 0.225 | 0.848 (0.644–1.117) | 0.787 (0.318–1.950) | <0.001 | 0.434 (0.361–0.522) | 0.435 (0.249–0.760) | |
| Radiotherapy (yes versus no) | 0.002 | 0.543 (0.362–0.814) | 0.876 (0.198–3.876) | <0.001 | 0.509 (0.348–0.745) | 0.642 (0.145–2.852) | |
| Targeted therapy (yes versus no) | 0.027 | 0.688 (0.488–0.971) | 0.126 (0.031–0.504) | 0.515 | 0.897 (0.642–1.253) | 0.870 (0.176–4.312) | |
| T3-4 versus T1-2 | 0.136 | 1.811 (0.802–4.087) | 1.422 (0.175–11.569) | 0.039 | 3.074 (0.982–9.620) | 1.217 (0.112–8.629) | |
| N1 versus N0 | 0.001 | 1.657 (1.214–2.262) | 2.394 (1.328–4.315) | <0.001 | 1.786 (1.305–2.445) | 2.428 (1.386–4.253) | |
| Size (⩾5 versus <5) | 0.277 | 1.200 (0.856–1.682) | 2.112 (1.236–3.608) | 0.958 | 1.008 (0.752–1.351) | 1.030 (0.607–1.747) | |
| Differentiation (G1-2 versus G3-4) | 0.109 | 1.410 (0.912–2.181) | 2.353 (1.015–5.456) | 0.908 | 1.022 (0.702–1.488) | 1.099 (0.531–2.276) | |
| CEA (⩾5 versus <5) | <0.001 | 1.590 (1.249–2.023) | 1.258 (0.647–2.445) | <0.001 | 1.722 (1.393–2.129) | 1.496 (0.808–2.772) | |
| CA199 (⩾37 versus <37)) | <0.001 | 1.824 (1.454–2.289) | 1.472 (0.879–2.465) | <0.001 | 1.799 (1.489–2.173) | 2.406 (1.468–3.943) | |
| Tumor location (right versus left) | 0.036 | 1.260 (1.007–1.577) | 1.056 (0.600–1.859) | 0.011 | 1.270 (1.051–1.535) | 1.021 (0.586–1.776) | |
| High-FPR versus low-FPR | <0.001 | 2.642 (2.084–3.351) | 1.994 (1.156–3.438) | <0.001 | 2.691 (2.186–3.312) | 2.786 (1.667–4.656) | |
Right-sided CRC was defined as the disease originating from ileocecal to transverse colon, whereas left-sided CRC comprised disease occurring in the splenic flexure, descending and sigmoid colon, as well as the rectum. p-value, p-value of univariable Cox regression; [1]: was adjusted by gender, age, tobacco, alcohol, diabetes, hypertension, chemotherapy, radiotherapy, T, N, differentiation, cancer size, CEA, CA 19-9 for tumor laterality or FPR; [2]: was adjusted by gender, age, tobacco, alcohol, diabetes, hypertension, chemotherapy, radiotherapy, T, N, differentiation, cancer size, CEA, CA199, and tumor laterality for H-FPR versus L-FPR; was adjusted by gender, age, tobacco, alcohol, diabetes, hypertension, chemotherapy, radiotherapy, T, N, differentiation, cancer size, CEA, CA 19-9, and FPR for right- versus left-tumor location; H- and L-FPR within stage I patient: FPR ⩾ 14.6 and FPR < 14.6 within stage I CRC patient; H- and L-FPR within stage I patient: FPR ⩾ 14.6 and FPR < 14.6 within stage I CRC patient; H- and L-FPR within stage II patient: FPR ⩾ 16.5 and FPR < 16.5 within stage II CRC patient; H- and L-FPR within stage I patient: FPR ⩾ 19.5 and FPR < 19.5 within stage III CRC patient; H- and L-FPR within stage IV patient: FPR ⩾ 22.8 and FPR < 22.8 within stage I CRC patient.
CA 19-9; carbohydrate antigen 19-9; CEA, carcinoembryonic antigen; CI, confidence interval; CRC, colorectal cancer; (H/L-) FPR, (high/low-) fibrinogen to prealbumin ratio; HR, hazard ratio; OS, overall survival; RFS, recurrence-free survival.